Weekly Updates #13

Tin W, Brunskill G, Kelly T, Fritz S. 15-Year Follow-Up of Recurrent “Hypoglycemia” in Preterm Infants. Pediatrics. 2012. A very long term follow up of a study by my friend Win Tin in the North East of England. They were unable to show an effect, no matter how they divided up the numbers, of recurrent hypoglycemia among preterm infants.

Grigsby PL, Novy MJ, Sadowsky DW, Morgan TK, Long M, Acosta E, et al. Maternal azithromycin therapy for Ureaplasma intraamniotic infection delays preterm delivery and reduces fetal lung injury in a primate model. Am J Obstet Gynecol. 2012(0). If you inject Ureaplasma into the amniotic fluid of rhesus monkeys they go into premature labour. If you treat them with azithromycin, premature delivery is prevented.

Miedema M, van der Burg PS, Beuger S, de Jongh FH, Frerichs I, van Kaam AH. Effect of Nasal Continuous and Biphasic Positive Airway Pressure on Lung Volume in Preterm Infants. J Pediatr. 2012(0). Increasing CPAP from 2 to 4 to 6 cmH2O increased lung volumes, and also increased tidal volumes in preterm infants, as measured by electrical impedance tomography. When infants on CPAP of 6 had BiPAP added (all this was using the InfantFlow SyPAP system) which was at an additional pressure of 3 cmH2O 50 times per minute for 0.5 seconds (non-synchromized) there was a very small further increase in lung volume, and no further increase in tidal volume. The authors were unable to consistently synchronise the device using the synchronisation module. In many parts of the world, medical devices, or new modes of ventilation can be introduced without any evidence that they are effective in improving clinical outcomes. BiPAP for preterm infants is one of those modes, this study suggests that clinical effects are unlikely with these settings.

Nyp M, Sandritter T, Poppinga N, Simon C, Truog WE. Sildenafil citrate, bronchopulmonary dysplasia and disordered pulmonary gas exchange: any benefits? J Perinatol. 2012;32(1):64-9. The authors gave sildenafil to 21 infants with BPD who also had pulmonary hypertension. They showed that according to the echocardiogram there was a reduction in pulmonary artery pressure, but there was no improvement in gas exchange after 48 hours of treatment. To be honest I don’t think that is the point; what we need to know is whether sildenafil improves survival and the long term. If the O2 needs don’t improve acutely, so what? There are may unknowns for these babies concerning the use of sildenafil, we need other good studies with clinical outcomes.

Stein H, Alosh H, Ethington P, White DB. Prospective crossover comparison between NAVA and pressure control ventilation in premature neonates less than 1500 grams. J Perinatol. 2012. This study only had 5 infants. They ventilated them with NAVA (where the ventilator is controlled by the diaphragmatic EMG) and with pressure control. The NAVA led to lower peak pressures but higher tidal volumes. Really who cares?We really need to know the comparisons between NAVA and volume ventilation, and whether there are clinically important differences.

Vento M, Cubells E, Escobar JJ, Escrig R, Aguar M, Brugada M, et al. Oxygen saturation after birth in preterm infants treated with continuous positive airway pressure and air: assessment of gender differences and comparison with a published nomogram. Archives of Disease in Childhood – Fetal and Neonatal Edition. 2012. Max Vento and his colleagues compared the pulse oximeter profiles of preterm infants who received CPAP in 21% oxygen to the published nomograms from infants who mostly did not receive CPAP. They showed that babies who get CPAP saturate higher, more quickly than published standards, especially the girls.

Ricci Z, Garisto C, Favia I, Vitale V, Di Chiara L, Cogo P. Levosimendan infusion in newborns after corrective surgery for congenital heart disease: randomized controlled trial. Intensive Care Medicine. 2012;38(7):1198-204. If you haven’t heard about levosimendan, you probably will…. It is an agent that sensitizes the myocardium to calcium, which has some theoretical value in the newborn who have reduced calcium sensitivity. It causes vasodilation and inotropism. This study randomized 63 babies to receive levosimendan or “standard post-op inotrope therapy”, which was as follows “… for CPB weaning consisted of milrinone (0.75 μg/kg/min) and dopamine (5 μg/kg/min) started at the end of cross clamp. If MAP was below 45 mmHg and filling pressures did not indicate the need for fluid replacement, dopamine was increased to 10 μg/kg/min. If such targets were not achieved, adrenaline (0.05–0.3 μg/kg/min) was added. Clinicians were allowed to decrease milrinone dose if MAP was lower than the selected cutoff after the addition of adrenaline.” The primary outcome of teh study was the development of Low Cardiac Output Syndrome, which is defined by them as “clinical signs and symptoms of the syndrome such as tachycardia (heart rate > 170 beats/min), oliguria (urine output < 0.5 mL/kg/h), cold extremities (peripheral temperature < 27 °C) with or without at least 30 % difference in arterial-mixed venous oxygen saturation or metabolic acidosis (an increase in the base deficit of greater than 4 or an increase in the lactate of more than 2 mg/dL) on two successive blood gas measurements. Postoperative cardiac arrest or the need for extracorporeal membrane oxygenation (ECMO) was also considered LCOS” Now that isn’t very clear to me, it looks like you could have LCOS just on the basis of tachycardia, or cool toes. In an unblinded study that is a bit of  a problem. the incidence of LCOS dropped from 61% to 37%, but it looks like none of the individual parts of the LCOS were different, in particular the mixed venous O2 was the same. The controls received more other inotropes than the Levosimendan group.

So I don’t know if this study really shows much effect of levosimendan, but it may be coming to an NICU near you, my colleague Po-Yin Cheung has published a few studies of levosimendan in newborn piglets, and showed that it has inotropic effects, in a hypoxia re-oxygenation model, with variable effects on regional perfusion. More work is needed before we start giving this widely in the NICU.

About keithbarrington

I am a neonatologist and clinical researcher at Sainte Justine University Health Center in Montréal
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